1. Field of the Invention
The present invention relates to novel 2- or 3-aryl substituted imidazo[1,2-a]pyridines of general formula: ##STR1## as described further below. The compounds of formula I are useful as local anesthetic agents, calcium channel blocking agents and antisecretory agents. Local anesthetics are known to exhibit antiarrhythmic activity. Calcium channel blocking agents are known to lower blood pressure. The compounds of Formula I may further be useful in ophthamology.
2. Description of the Prior Art
No examples of local anesthetics with a 2- or 3-aryl substituted imidazo[1,2-a]pyridine structure have been seen in the prior art.
Local anesthetics are drugs which reversibly block nerve conduction near their site of application or injection and thus produce temporary loss of feeling or sensation in a limited area of the body. Local anesthetics are used to prevent pain in surgical procedures, injury, and disease. Local anesthetics can act on any part of the nervous system and on every type of nerve fiber. Since ionic mechanisms of excitability are similar in nerve and muscle, it is not surprising that local anesthetics also have prominent actions on all types of muscular tissue.
Local anesthetics prevent both the generation and the conduction of a nerve impulse. The main site of action is the cell membrane, and there is seemingly little direct action of physiological importance on the axoplasm. The axoplasmic effects that do occur may be secondary to the membrane action.
Known local anesthetics block conduction by interfering with the fundamental process in the generation of a nerve action potential, namely, the large transient increase in the permeability of the membrane to sodium ions that is produced by a slight depolarization of the membrane.
One theory of how local anesthetics block nerve conduction is that they compete with calcium at some site that controls the permeability of the membrane. Local anesthetics also reduce the permeability of resting nerve to potassium as well as to sodium ions.
Adverse reactions to local anesthetics can be divided into two groups: systemic and local adverse reactions. Systemic adverse reactions are usually associated with high blood levels of the drug and usually result from overdosage, rapid systemic absorption, or inadvertent intravenous administration. The reactions usually involve the central nervous and cardiovascular systems. Local adverse reactions to known local anesthetic drugs are either cytotoxic or allergic.